Isolation and characterisation of human gingival margin-derived STRO-1/MACS+ and MACS− cell populations

Recently, gingival margin-derived stem/progenitor cells isolated via STRO-1/magnetic activated cell sorting (MACS) showed remarkable periodontal regenerative potential in vivo. As a second-stage investigation, the present study's aim was to perform in vitro characterisation and comparison of the stem/progenitor cell characteristics of sorted STRO-1-positive (MACS+) and STRO-1-negative (MACS−) cell populations from the human free gingival margin. Cells were isolated from the free gingiva using a minimally invasive technique and were magnetically sorted using anti-STRO-1 antibodies. Subsequently, the MACS+ and MACS− cell fractions were characterized by flow cytometry for expression of CD14, CD34, CD45, CD73, CD90, CD105, CD146/MUC18 and STRO-1. Colony-forming unit (CFU) and multilineage differentiation potential were assayed for both cell fractions. Mineralisation marker expression was examined using real-time polymerase chain reaction (PCR). MACS+ and MACS− cell fractions showed plastic adherence. MACS+ cells, in contrast to MACS− cells, showed all of the predefined mesenchymal stem/progenitor cell characteristics and a significantly higher number of CFUs (P<0.01). More than 95% of MACS+ cells expressed CD105, CD90 and CD73; lacked the haematopoietic markers CD45, CD34 and CD14, and expressed STRO-1 and CD146/MUC18. MACS− cells showed a different surface marker expression profile, with almost no expression of CD14 or STRO-1, and more than 95% of these cells expressed CD73, CD90 and CD146/MUC18, as well as the haematopoietic markers CD34 and CD45 and CD105. MACS+ cells could be differentiated along osteoblastic, adipocytic and chondroblastic lineages. In contrast, MACS− cells demonstrated slight osteogenic potential. Unstimulated MACS+ cells showed significantly higher expression of collagen I (P<0.05) and collagen III (P<0.01), whereas MACS− cells demonstrated higher expression of osteonectin (P<0.05; Mann–Whitney). The present study is the first to compare gingival MACS+ and MACS− cell populations demonstrating that MACS+ cells, in contrast to MACS− cells, harbour stem/progenitor cell characteristics. This study also validates the effectiveness of the STRO-1/MACS+ technique for the isolation of gingival stem/progenitor cells. Human free gingival margin-derived STRO-1/MACS+ cells are a unique renewable source of multipotent stem/progenitor cells

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

Epstein-Barr Virus Infection and Sporadic Breast Cancer Risk: A Meta-Analysis

BACKGROUND: A large number of epidemiological studies have evaluated the association between Epstein-Barr virus infection and breast carcinoma risk but results have been inconsistent. METHODOLOGY: Research using the polymerase chain reaction technique for detecting the Epstein-Barr virus was selected; 24 studies and 1535 cases were reviewed. Information on the study populations, sample types, publication calendar period and histological types of breast carcinoma were collected. An unconditional logistic regression model was used to analyze potential parameters related to the Epstein-Barr virus prevalence. A Kappa test was used to evaluate the consistency in detecting different Epstein-Barr virus DNA regions. Nine studies that included control groups and 1045 breast cancer cases were adopted in this meta-analysis. CONCLUSIONS: We found that 29.32% of the patients with breast carcinoma were infected with the Epstein-Barr virus. The prevalence of Epstein-Barr was highest in Asia (35.25%) and lowest in the USA (18.27%). Statistical analysis revealed a trend that showed lobular breast carcinoma might have the strongest association with Epstein-Barr virus infection. This meta-analysis showed a significant increase in breast malignancy risk in patients testing positive for the Epstein-Barr virus (OR = 6.29, 95% CI = 2.13-18.59). This result suggests that an Epstein-Barr virus infection is statistically associated with increased breast carcinoma risk

Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

International audienceAlthough a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation

Predictors of packed red cell transfusion after isolated primary coronary artery bypass grafting – The experience of a single cardiac center: A prospective observational study

<p>Abstract</p> <p>Background</p> <p>Preoperative patients' characteristics can predict the need for perioperative blood component transfusion in cardiac surgical operations. The aim of this prospective observational study is to identify perioperative patient characteristics predicting the need for allogeneic packed red blood cell (PRBC) transfusion in isolated primary coronary artery bypass grafting (CABG) operations.</p> <p>Patients and Methods</p> <p>105 patients undergoing isolated, first-time CABG were reviewed for their preoperative variables and followed for intraoperative and postoperative data. Patients were 97 males and 8 females, with mean age 58.28 ± 10.97 years. Regression logistic analysis was used for identifying the strongest perioperative predictors of PRBC transfusion.</p> <p>Results</p> <p>PRBC transfusion was used in 71 patients (67.6%); 35 patients (33.3%) needed > 2 units and 14 (13.3%) of these needed > 4 units. Univariate analysis identified female gender, age > 65 years, body weight ≤ 70 Kg, BSA ≤ 1.75 m², BMI ≤ 25, preoperative hemoglobin ≤ 13 gm/dL, preoperative hematocrit ≤ 40%, serum creatinine > 100 μmol/L, Euro SCORE (standard/logistic) > 2, use of CPB, radial artery use, higher number of distal anastomoses, and postoperative chest tube drainage > 1000 mL as significant predictors. The strongest predictors using multivariate analysis were CPB use, hematocrit, body weight, and serum creatinine.</p> <p>Conclusion</p> <p>The predictors of PRBC transfusion after primary isolated CABG are use of CPB, hematocrit ≤ 40%, weight ≤ 70 Kg, and serum creatinine > 100 μmol/L. This leads to better utilization of blood bank resources and cost-efficient targeted use of expensive blood conservation modalities.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially